Early Phase I Study of a 99mTc-Labeled Anti–Programmed Death Ligand-1 (PD-L1) Single-Domain Antibody in SPECT/CT Assessment of PD-L1 Expression in Non–Small Cell Lung Cancer
| Autor: | Jim O’Doherty, Changchun Liu, Levente K. Meszaros, Nicholas C.L. Wong, Jinhua Zhao, Lingzhou Zhao, Yan Xing, Gitasha Chand, Hong Hoi Ting, Gary Cook |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
PD-L1 Adult Male Lung Neoplasms Single Photon Emission Computed Tomography Computed Tomography medicine.medical_treatment Biopsy single domain antibody (sdAb) B7-H1 Antigen 03 medical and health sciences Clinical 0302 clinical medicine non–small cell lung cancer Spect imaging Carcinoma Non-Small-Cell Lung medicine Humans Radiology Nuclear Medicine and imaging Histidine Lung cancer Radiometry Aged biology business.industry Technetium Immunotherapy SPECT/CT Middle Aged medicine.disease Primary tumor Immunohistochemistry 3. Good health early phase I 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Lymphatic Metastasis biology.protein Female Bone marrow Antibody business Nuclear medicine Oligopeptides |
| Zdroj: | Journal of Nuclear Medicine Xing, Y, Chand, G, Liu, C, Cook, G J R, O'Doherty, J, Zhao, L, Wong, N, Meszaros, L, Ting, H H & Zhao, J 2019, ' Early Phase I Study of a 99m Tc-Labeled Anti-Programmed Death Ligand-1 (PD-L1) Single-Domain Antibody in SPECT/CT Assessment of PD-L1 Expression in Non-Small Cell Lung Cancer ', Journal of Nuclear Medicine, vol. 60, no. 9, pp. 1213-1220 . https://doi.org/10.2967/jnumed.118.224170 |
| ISSN: | 1535-5667 0161-5505 |
| Popis: | Immunotherapy with checkpoint inhibitor programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies demonstrates improvements in treatment of advanced non–small cell lung cancer. Treatment stratification depends on immunohistochemical PD-L1 measurement of biopsy material, an invasive method that does not account for spatiotemporal heterogeneity. Using a single-domain antibody, NM-01, against PD-L1, radiolabeled site-specifically with 99mTc for SPECT imaging, we aimed to assess the safety, radiation dosimetry, and imaging characteristics of this radiopharmaceutical and correlate tumor uptake with PD-L1 immunohistochemistry results.Methods: Sixteen patients (mean age, 61.7 y; 11 men) with non–small cell lung cancer were recruited. Primary tumor PD-L1 expression was measured by immunohistochemistry. NM-01 was radiolabeled with [99mTc(OH2)3(CO)3]+ complex binding to its C-terminal hexahistidine tag. Administered activity was 3.8–10.4 MBq/kg, corresponding to 100 μg or 400 μg of NM-01. Whole-body planar and thoracic SPECT/CT scans were obtained at 1 and 2 h after injection in all patients, and 5 patients underwent additional imaging at 10 min, 3 h, and 24 h for radiation dosimetry calculations. All patients were monitored for adverse events.Results: No drug-related adverse events occurred in this study. The mean effective dose was 8.84 × 10−3 ± 9.33 × 10−4 mSv/MBq (3.59 ± 0.74 mSv per patient). Tracer uptake was observed in the kidneys, spleen, liver, and bone marrow. SPECT primary tumor–to–blood-pool ratios (T:BP) varied from 1.24 to 2.3 (mean, 1.79) at 1 h and 1.24 to 3.53 (mean, 2.22) at 2 h (P = 0.005). Two-hour primary T:BP ratios correlated with PD-L1 immunohistochemistry results (r = 0.68, P = 0.014). Two-hour T:BP was lower in tumors with ≤1% PD-L1 expression (1.89 vs. 2.49, P = 0.048). Nodal and bone metastases showed tracer uptake. Heterogeneity (>20%) between primary tumor and nodal T:BP was present in 4 of 13 patients.Conclusion: This first-in-human study demonstrates that 99mTc-labeled anti–PD-L1-single-domain antibody SPECT/CT imaging is safe and associated with acceptable dosimetry. Tumor uptake is readily visible against background tissues, particularly at 2 h when the T:BP ratio correlates with PD-L1 immunohistochemistry results. |
| Databáze: | OpenAIRE |
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